Exam 5 (GI Tract) Flashcards
What organ does most of absorption
Small intestine
Immune defenses of GI tract
Low pH of stomach.
Intestinal luminal bacteria.
Mucosa-associated lymphoid tissue (MALT) like Peyer’s patches have T cells and B cells
Parasympathetic actions on GI tract
vagus and pelvic nerves
increase smooth muscle activities
Relax sphincters
Sympathetic actions on GI tract
Celiac and mesenteric ganglia.
Decrease motility.
Causes sphincters to contract.
Inhibits secretion of digestive enzymes
Hirschsprung disease
missing part of myenteric plexus usually in large intestine.
Causes spasm of affected segment.
Causes stool to fill afffected segment.
What neurotransmitter is generated in submucosal plexus
Acetylcholine
What would cholinergic medications cause
Cramping and diarrhea
What would anticholinergic medications cause
Dry mouth and constipation
What are the three salivary glands of mouth
Parotid
Submandibular
Sublingual
Amylase
In saliva
Breaks down starch.
Also released from pancreas exocrine
Lingual Lipase
In saliva
Breaks down fats
ph of saliva
7.0
When is saliva production inhibited
Sleep
Fear
What starts peristaltic activity in esophagus
Distension of esophagus (spreading of esophagus causes it to contract to move food towards stomach.)
What part of nervous system controls peristalsis and sphincter tone
Enteric nervous system
What part of nervous system is the upper esophagus
extrinsic nervous system
Cardia
Accepts food from esophagus
Fundus
Where food collects in stomach
Body of stomach
Where food is churned and mixed
Pylorus
Releases food from stomach into duodenum
Ruggae
Folds of stomach to increase surface area
Surface cells of stomach secretions
Bicarbonate
Mucus
Parietal cells of stomach secretions
HCl
Intrinsic factor
Intrinsic factor
Secreted by parietal cells of stomach
Binds to vitamin B12 in stomach
Chief cells of stomach secretions
Pepsinogen
Gastric lipase
Enterochromaffin-like (ECL) cells of stomach
Secrete histamine
G cells of stomach
Secrete gastrin in response to peptides
Gastrin
Secreted by G-cells of antrum of stomach and duodenum
Stimulate parietal cells to make HCL
Stimulated in response to peptides.
Negative feedback by low pH
D-cells of stomach
Secrete somatostatin in response to acid in lumen.
Somatostatin
Secreted by D-cells of stomach
Stimulated to response to acid in lumen
Inhibits acid secretion
Inhibit gastrin release
Inhibit histamine release
Turns everything off (party pooper)
Proton Pump Inhibitors
Medicine that binds irreversibly to H+/K+ pump pf parietal cells to inhibit the secretion of H+
What all does the vagus nerve stimulate to happen in stomach
Acid secretion from parietal cells.
Histamine secretion from ECL cells
What does gastrin stimulate in stomach
Histamine release form ECL cells that then directly stimulates parietal cells to make HCl
List small intestine parts proximal to distal
Duodenum
Jejunum
Illeum
(DJ Illeum🎧🎶💿🎹)
Microvilli
Cillia of epithelium of small intestine to increase surface area. Helps form the brush border
Brush border of small intestine
Microvilli
Villi
Crypts
Paneth cells
Goblet cells
Digestive enzymes
Intestinal crypt
Small valleys next to villi of small intestine to make even more surface area
Goblet cells
Secret mucus in small intestine
Paneth cells
secrete antimicrobial peptides
CCK
Cholecystokinin.
Relaxes Sphincter of Oddi and causes gallbladder t contract to secrete bile into duodenum of small intestine.
Also promotes secretion of digestive enzymes of the pancreas into the duodenum
Secretin
Produced in duodenum in response to acid in duodenum.
Increases bicarbonate production from pancrease
Gastric inhibitory peptide
Produced in duodenum and jejunim in response to glucose and fat in duodenum.
Stimulates insulin secretion
Vasointestinal Peptide
Neurotransmitter.
Stimulates intestinal secretion of electroyltes and water.
Motilin
Secreted by ECL cells in stomach, small intestine, and colon.
Induces smooth muscle contraction between meals
Serotonin
Secreted by ECL cells of brush border in response to distention of gut wall.
Mostly excitatory and increases GI motility
Neuroendocrine carcinoid tumor
Causes oversecretion of serotonin.
Causes flushing, diarrheaa, bronchospasm, cardiac valvular disease.
Somatostatin used to help symptoms by decreasing release of serotonin
Breakdown of starch
Salivary and pancreatic amylase convert it to oligosaccharides.
Enzymes of luminal wall of intestines break down oligosaccharides and disacharides
Breakdown of protein
Pepsin in stomach.
Then pancreatic elastase, trypsin, and chymotrypsin
Breakdown of fat
Lipases from mouth, stomach and pancreas.
Emulsion formation with bile
What all is absorbed in small intestine and how
Monosaccharides via Na-coupled cotransport and diffusion.
Amino acids via sodium or hydrogen coupled transporters.
Lipds via transport proteins as long-chain fatty acids
Where does most fluid absorption of food happen
ascending colon.
Jobs of large intestine
Fluid absorption.
Bacterial fermentation
Production of vitamin K
Deconjugation of bile acid to return to portal circulation.
Fermentation of fiber into short chain fatty acids.
Storage and elimination of waste
Haustra
Segments of large intestine.
More active on left side to slow down feces before excretion.
(Pump the breaks I’m about to shit myself)
Largest organ in body (besides skin)
Liver
Primary functions of liver
Filtration and storage of blood.
Metabolism.
Detoxification.
Plasma protein production.
Bile formation.
Bilirubin metabolism.
Regeneration (regenerates itself)
Hepatic lobules
Basic functional unit of liver
Hepatocytes
Liver cells.
80% of liver mass.
Produce bile
Synthesize proteins.
Metabolize carbs, lipids, proteins, drugs.
Detoxify substances.
Store vitamins, minerals, and glycogen.
Sinusoids
Capillaries in lobules of liver.
Lined with Kupffer cells.
Filter blood.
Immune response.
Have stellate (Ito) cells
Kupffer cells
In sinusoids of liver
Macrophages of liver
Stellate (Ito) cells
In sinusoids of liver
Store vitamin A.
Play roles in fibrosis and regulation of blood flow
Bile canaliculi
Small ducts between hepatocytes that collect bile.
Merge to form bile ducts.
Connective tissue of liver
Separates lobules to keep everything compartmentalized and gives structure
Portal vein system
Carries blood from GI tract to liver to be filtered.
Blood then goes through hepatic veins and into inferior vena cava
Liver job in carb metabolism
Glycogen storage when blood sugar high.
Gluconeogenesis when blood sugar low
Liver job in lipid metabolism
Stores and makes lipids.
Ketogenesis
Ketogenesis
Converts fatty acids to ketone bodies for energy
Protein metabolism in liver
Synthesis of plasma proteins.
Amino acid metabolism
Amonia detoxification.
Amonia detoxification in liver
Turns amonia from breakdown of amino acid into urea to be pissed out.
What plasma proteins does the liver synthesize
ALBUMIN
Clotting factors
Lipoproteins
What regulates the fed state and what happens
INSULIN helps glucose enter cell and liver will stor glucose, make energy or make fat.
What regulates the fasting state and what happens
GLUCAGON, epinephrine, and cortisol
Glycogenolysis to put glucose into blood.
Gluconeogenesis
Lipoproteins
Transport lipids in circulation
Cholesterol
Made in liver.
Precursor for steroid hormones.
Cell membrane component.
Converted into bile acids/salts
Excess removed through bile
Protein metabolism
Steak –> proteins–> AA–> absorbed into blood –> liver ant tissue.
Can be turned into enzymes, hormones, glucose, or fatty acids
Nonessential AA
formed by liver
Albumin
Most common plasma protein.
Made by liver.
Maintains oncotic pressure.
Transports stuff in blood
Transport proteins made by liver
Transferrin (iron)
Ceruplasmin
Haptoglobin (eat RBC fragments)
Thyroxine binding globulin
Clotting factors made by liver
I, II, V, XII, IX, X, XI, XII, XIII.
Protein C and S.
Antithrombin.
Many vitamin K dependent
Acute phase proteins made by liver
Respond to inflammation.
CRP
Serum amyloid A
Fibrinogen
Alpha-1 antitrypsin.
Haptoglobin.
Ferritin.
Binding proteins made by liver
Sex hormone binding globulin.
Corticosteroid binding globulin.
Enzymes made by liver.
AST/ALT used in AA metabolism.
Angiotensinogen
Proteins made by liver
Albumin
Clotting factors
Transport proteins
Acute phase proteins
Complement
Binding proteins
Enzymes
Lipoproteins made by liver
VLDL
HDL
VLDL
Very low density lipoproteins.
Transport triglycerides from liver to peripheral tissues.
Converted to IDL in bloodstream and to LDL in liver.
HDL
High density lipoproteins.
Reverse cholesterol transport (from tissues back to liver)
Hormones made by liver
IGF-1
Thrombopoietin
Hepcidin for iron absorption
Ferroportin transports iron out of cell
Storage protein made by liver
Ferritin
Ceruplasmin
Phase I rxn of liver
Cytochrome P450 enzymes catalyze hydroxylation rxns to make drug more water soluble
Phase II rxn of liver
Conjugation of hydrophilic substance onto drug to make it more water soluble.
Phase III rxn of liver
Transport of substrate into either bile or blood for excretion
What is billirubin made of
80% Broken down hemoglobin and 20% turnover of heme from other tissues
Billirubin metabolism
Unconjugated (indirect) billirubin turned into conjugated (direct)
Bile
Made by liver and stored in gallbladder to be released into duodenum.
Used for digestion and absorption of fats and fat-soluble vitamins (ADEK) in small intestine.
What makes up bile
Bile salts
Bile acids
Phospholipids
Cholesterol
Bilirubin
Electrolytes
Sphincter of Oddi
Sphincter between liver/gallbladder and duodenum of small intestine.
Also controls flow of pancreatic juice into duodenum
What nutrients does the liver store
Glycogen.
Vitamins ADEK and B12
Iron
Copper
What hormones are metabolized in liver
ESTROGEN (makes guys have tits if not metabolized)
Insulin
Glucagon
Cortisol
What hormones are secreted or activated by liver
IGF-1
Hepcidin
Vitamin D
T4–>T3
Alanine aminotransferase (ALT)
Liver enzyme
Mostly in hepatocytes.
Assist gluconeogenesis and AA metabolism.
Hepatocyte injury puts ALT into blood
Aspartate Aminotransferase (AST)
Liver enzyme
Assist urea cycle and AA metabolism in hepatocytes.
Hepatocyte injury puts AST into blood.
How can a hepatocyte injury be seen in lab blood work
ALT and AST will be elevated
Alkaline phosphatase (ALP)
Liver enzyme
Increases concentration in bile ducts, liver, bones, and placenta.
Removes phosphate groups from various molecules.
Increased levels in blood indicate ductal damage (cholestasis, liver damage, bone damage.
Gamma-Glutamyl Transferase
Liver enzyme.
“Another ALP”
Does metabolism of glutathione in bile ducts, liver, and kidneys.
Increased levels in blood indicate bile duct disfunction/cholestasis as well as alcohol use
Lactate dehydrogenase
Liver enzyme.
found everywhere.
Cholestasis
Reduction or stop of bile flow
Where does bile flow when sphincter of Oddi is closed
Gallbladder
Where does bile flow when sphincter of Oddi is open
Duodenum of small intestine
Function of gallbladder
Store and concentrate bile.
Concentrated 3-10 fold by removal of water and electrolytes
What determines if bile goes into gallbladder or duodenum from liver
Pressure of gallbladder, liver, and sphincter of Oddi.
It will always flow from high to low pressure
How much bile reenters portal vein to return to liver
95%
How much bile released from gallbladder is excreted in feces
5%
Exocrine part of pancreas
Acinar cells
Endocrine part of pancreas
Islets of Langerhans
Islet of langerhans
Endocrine part of pancreas.
All throughout pancreas.
More common in tail than head or body.
Secrete glucagon (alpha) insulin (beta), somatostatin (delta), pancreatic peptide (F)
Insulin
Secreted by beta cells of pancreas.
Anabolic.
Increases the storage of glucose, fatty acids, and amino acids.
Lowers blood sugar by inhibiting gluconeogenesis, glycogenolysis, and lipolysis.
Stimulated by high blood sugar.
Promotes, glucose uptake by cells, glycogenesis, lipogenesis, protein synthesis
Glucagon
Secreted by alpha cells of pancreas.
Catabolic.
Mobilizes glucose, fatty acids, and amino acids into blood stream.
Raises blood sugar by stimulating glycogenolysis, gluconeogenesis, and lipolysis
Stimulated by low blood sugar
How does glucose get into B cell
GLUT transporters
Calcium
Makes stuff happen.
Pulls the trigger on everything
Insulin synthesis
Made in rough ER of B cell.
Transported to golgi.
Packaged into membrane-bound granules.
Granules move to plasma membrane for exocytsis.
Crosses over capillary endothelium into blood stream and acts quickly
Half life of insulin
5 mins. (very short)
Is secretion of insulin part of sympathetic or parasympathetic
Parasympathetic
Insulin relationship with potassium
Insulin causes K to enter cell causing extracellular K to decrease.
So pts with insulin infusions often develop hypokalemia
Type 1 diabetes
Autoimmune destruction of beta cells
Type 2 diabetes
Dysregulation of insulin release from B cells and increases of insulin resistance of peripheral tissue.
Leads to eventual B cell death
Effects of hyperglycemia
Hyperosmolality of blood.
Glucose spills out into blood.
Water follows glucose causing water loss, dehydration, polydipsia
Exocrine function of pancreas
Produces 1.5 liters of digestive enzymes.
Amylase
Protease
Lipase
Carboxypeptidase
Ribonuclease
Deoxyribonuclease
Phospholipase A
Trypsinogen
Chymotrypsinogen
Procarboxypolypeptidase
Trypsin
Activates everything.
So converting trypsinogen (made by pancreas, exocrine) into active form trypsin gets everything going
Zymogen
Inactive form of enzyme
Maltase
Breaks maltose into two glucose
Sucrase
Breaks sucrose into glucose and fructose
Lactase
Breaks down lactose into glucose and galactalose
What stimulates release of CCK
Fatty acids and Amino acids
Where is vitamin B12 absorbed
Illeum but must be bound with intrinsic factor from parietal cells of stomach
What BMI is overweight
25-29.9
What BMI is underweight
<18.5
What is a healthy BMI
18.5-24.9
BMI for Obesity class 1
30-34.9
BMI for Obesity Class 2
35-39.9
BMI for Morbid Obesity
> 40
What waist length is related to increased risk of diabetes, HTN, CAD
> 35 inches in women
40 inches in men
Where to measure waiste circumference
Uppermost point on iliac crest
What waist to hip ratio is increased risk for weight related problems in men
> 1.0
What waist to hip ratio is increased risk for wait related problems in women
> 0.85
Estimated Average Requirement (EAR) of dietary intake
Indicator of adequacy to meet needs of half of the healthy individuals in a life stage
Recommended Daily Allowance (RDA) of dietary intake
Average requirement plus two standard deviations. Established to prevent deficiency in healthy people, not inhance health
Adequate intake (AI)
Estimated intake of healthy population
Tolerable Upper Limit (TUL) of dietary intake
Upper limit unlikely to pose a risk of adverse health effects.
Steps of nutritional therapy
Evaluate
Assess
Determine
Monitor
Validate
Carbohydrates
4kcal/g
50-60% calorie intake
main source of energy
Stored as glycogen in liver and muscle
Enhance learning and memory
Proteins
4 kcal/g
About 20% calorie intake.
Need about 1g/kg per day
SUpport muscle mass
Used in cell walls, enzymes, hormones peptides, antibodies.
Fuel source
Fats
9 kcal/gram
Main source of energy STORAGE/adiposity
Vehicle for fat soluble vitamins
Makes up cell membranes and hormones
Source of essential fatty acids
Less than 30% calorie intake
Makes food taste good and you feel full
Fiber
Should get 25g per day
Usually we only get like 10
Essential amino acids
Must be eaten bc we can’t make them.
PVT TIM HLL
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Leucine
Lysine
Positive nitrogen balance
Indicates an anabolic state
Negative nitrogen balance
Indicates a catabolic state.
Ideal Nitrogen balance
+1-+4
What controls apetite
Hypothalamus
Limbic system role in apetite
Controls reward and motivation.
Plays role in addition
Neural connection between gut and brain
Vagus nerve
Ghrelin
Made in stomach
Stimulates appetite in response to no food.
Promotes weight gain.
Acts on hypothalamus
What surgery reduces ghrelin levels
Gastric bypass surgery
Leptin
Made in adipocytes.
Acts on hypothalamus to decrease appetite in feedback mechanism.
Signals adequate energy stores in puberty.
Stimulates sympathetic nervous system to use energy.
Leptin resistance could be linked to leptin
Glucagon Like peptide (GLP-1)
Made by intestinal L-cells
Antagonizes CB1 receptors causing decreased feeding, weight loss, incretin effect on insulin secretion.
Used to treat diabetes and obesity
Peptide YY
Released by jejunum in response to fat
Decreases food intake
Inhibits gastric acid secretion.
Inhibits stomach motility.
Oxyntomodulin
Induces satiety.
Increases energy expendature.
Decreases weight.
Adiponectin
Secreted by adipocytes in response to fasting.
Makes cells more sensitive to insulin and increases fatty acid oxidation.
Decreases visceral fat mass.
List of macrominerals (major minerals)
Calcium
Chloride
Phosphorus
Potassium
Sulfur
Sodium
Magnesium
Sodium function
Maintain fluid balance.
Maintain acid-base balance
Nerve, muscular impulse conduction
Sodium deficiency
Hyponatremia.
Headache
seizure
encephalopathy
Muscle twitching
Sodium toxicity
Hypernatremia
Agitation
Coma
Sodium supplementation
Needed in excess sweat.
Needed in addison’s disease
Potassium function
Conduction of nerve impulses
Muscle contractions
Potassium deficiency
Hypokalemia
Weakness
Diminished reflexes
paresthesia
Arrhythmia
Potassium toxicity
Hyperkalemia
Seen in renal failure.
Abdominal cramping
Arrhythmia
Cardiac arrest
Potassium supplementation
Only for accelerated losses
Calcium function
Bone mineralization.
Muscle contraction
Blood clotting
Calcium deficiency
Hypocalcemia
Chronic is osteoperosis.
Acute is irritability, paresthesia, tetany, seizure
Calcium toxicity
Seen in hyperparathyroidism and cancers
Calcium supplementation
Calcium citrate more easily absorbed bc more acidic but calcium carbonate has more calcium
Phosphorus function
In bones and teeth.
DNA
RNA
ATP
ADP
Phosphorus deficiency
Bone loss
Muscle weakness
Refeeding syndrome
Phosphorus toxicity
Renal disease.
Treated with phosphate binders to stop absorption
Phosphorus supplementation
None
Iron function
Oxygen delivery
In hemoglobin, myoglobin, and cytochromes
Iron deficiency
Weakness, fatigue, SOB, microcytic anemia.
Developmental delays
Pallor
Clubbed nails
Iron toxicity
Liver failure (first organ effected)
Hemochromatosis.
Iron supplementation
Iron sulfate.
IV dextran.
Injectafer )ferric carboxymaltose
Iodine function
Synthesis of thyroid hormone
Iodine deficiency
Cretinism
Goiter
Iodine toxicity
Acne
Goiter
Thyroiditis
Iodine supplementation
None in US bc we have iodized salt
Fluoride function
Protects teeth against dental carries.
Bone mineralization
Fluoride deficiency
lack of fluoride in water sources
Fluoride toxicity
Can disrupt tooth enamel
Fluoride supplementation
Water supply
Tooth paste
Get it painted on teeth at dentist
Zinc function
Component of enzymes, DNA, RNA
Collagen formation
Immunity
Zinc deficiency
Growth retardation
Alopecia
Eczema
Loss of taste
Impaired immunity
Zinc toxicity
Metallic taste
Anosmia
Inhibits copper absorption
Zinc supplementation
In cold lozenges
Fat soluble vitamins
ADEK
Vitamin A function
Development and maintenance of mucus membranes and skin.
Plays role in vision and gonad function
Vitamin A deficiency
Hyperkeratosis.
Night blindness.
Xeropthalmia
Vitamin A toxicity
Tetratogenic acne medicine
Vitamin A supplementation
Not reccomended bc caould increase cancers
Vitamin D Function
Calcium phosphorus regulation.
Immunity.
Neuromuscular function
Vitamin D deficiency
Rickets.
Osteomalacia.
Vitamin D toxicity
Rare
Calcitriol
Active form of vitamin D from kidney
Calcidiol
Inactive form of vitamin D from liver
Vitamin D supplementation
D2 from food
D3 from sun
Vitamin E functino
Antioxidant.
Inhibits platelet aggregation
Vitamin E deficiency
Rare.
Muscle weakness and weak immune system
Vitamin E toxicity
Interfere with vitamin K formation of clotting factors
Vitamin E supplementation
Roles in heart disease and cancer
Vitamin K function
Cofactor for enzymes required for coagulation factors
Vitamin K deficiency
Bruising
Mucosal bleeding
Melena
Hematuria
Vitamin K toxicity
No TUL
Person on warfarin needs consistent daily dose
Vitamin K supplementation
Infants given injections at birth.
Sometimes used therapeutically for warfarin overdose.
Vitamin C (ascorbic acid) function
Antioxidant
Collagen formation.
Aids in iron reabsorption
Vitamin C (ascorbic acid) deficiency
Scurvy
Seen in smokers, alcoholics, and pirates.
Elderly risk due to lack of fruits and vegetables
Vitamin C (ascorbic acid) toxicity
NVD
Abdominal pain
Vitamin C (ascorbic acid) supplementation
Used as antioxidant
Treat cold
Vitamin B1 (thiamin) function
Essential for enzymes of energy production
Vitamin B1 (thiamin) deficiency
Primary is Beriberi.
Impaired absorption is Wenicke’s encephalopathy.
Poor appetite, irritability, apathy, confusion, weight loss, clonus, neuropathy
Vitamin B1 (thiamin) toxicity
None
Vitamin B1 (thiamin) supplementation
In fortified grains.
Given in IV when treating alcoholic
Vitamin B3 (niacin) function
DNA synthesis
Energy metabollsim
Skin, GI tract, Nervous system
Vitamin B3 (niacin) deficiency
Pellegra
4Ds: diarrhea, dermatitis, dementia, death
Found in corn based diets
Vitamin B3 (niacin) toxicity
Flushing and dizziness.
Major adverse cardiac events
Vitamin B3 (niacin) supplementation
Made from tryptophan so usually don’t need supplements
Vitamin B5 (pantothenic acid) function
Assist in fatty acid synthesis via coenzyme A
Vitamin B5 (pantothenic acid) deficiency
Burning feet syndrome
Vitamin B5 (pantothenic acid) toxcity
none
Vitamin B5 (pantothenic acid) supplementation
Not needed in healthy adults.
Can get from eating eggs.
Vitamin B6 (pyridoxine) function
Coenzyme in metabolism of amino acids
Treat pregnancy associated nausea.
Vitamin B6 (pyroxidine) deficiency
Glossitis
Cheilosis
Dermatits
Neuropathy
Vitamin B6 (pyridoxine) toxicity
Neuropathy
blindness
Vitamin B9 (folic acid) function
Essential for formation of DNA RNA heme.
Conversion of homocysteine to methionine
Vitamin B9 (folic acid) deficiency
Neural tube defects
Vitamin B9 (folic acid) Toxicity
Can make B12 deficiency
Vitamin B12 (Cobalamin) function
Cell replication and neurologic function
Vitamin B12 (cobalamin) deficiency
Megaloblastic anemia.
Pernicious anemia.
Neuropathy.
Seen in vegetarians and elderly
Vitamin B12 (cobalamin) toxicity
not documented
Vitamin B 12 (cobalamin) supplementation
From Animal sources.
Pernicious anemia
Lack of intrinsic factor.
Can cause deficiency of B12
Biotin function
Coenzyme in synthesis of fat, glycogen, and amino acids
Biotin deficiency
Alopecia
Dermatiis
Paresthesia
Biotin toxicity
Rare
Can interfere withs some lab tests like troponin
Biotin supplementation
Usually not needed
Peptide hormones
Pancreas
Pituitary
Parathyroid
Gastrointestinal
Made as prohormones
Active hormones stored in intracellular vesicles
Mostly water soluble so don’t require carrier molecules in blood
Amine hormones
Catecholamines and thyroidd hormones.
Tyrosine based
Catecholamines are water soluble.
Thyroid hormones not water soluble so need carrier protein in blood
Steroid hormones
Made from cholesterol
Rapidly diffuse once synthesized due to high lipid solubility.
Needs carrier protien in blood
Primary disorder
Excess or deficiency of secretion by target gland
Secondary disorder
Excess or deficiency of secretion by pituitary
Tertiary disorders
Excess or deficiency of secretion by hypothalamus
Dynamic/provacative hormone test
Measures changes in hormone levels in response to stimulus
Hypothalamus jobs
Control HR, temp, appetite, thirst, sleep cycle
Hypothalamic hormones
ADH
OT
CRH
TRH
GHRH
GHIH (somatostatin)
GnRH
PRH
Dopamine (prolactin inhibiting)
Antidiuretic hormone (ADH) (Vasopressin)
Controls water Balance
Combats dehydration.
Release stimulated by decreased blood volume or increases in serum osmolality.
Stimulates thirst via hypothalamus
ADH receptors
V1 in vascular smooth muscle
V2 in kidneys
Oxytocin (OT)
Stimulates uterine contraction in parturition in positive feedback mechanism.
Stimulates milk let down and ejection.
Promotes maternal and social bonding.
Prostate health and disease
What hormones come from posterior pitutary
ADH
OT
Prolactin
Controls milk production from ant pit
How do hypothalamic hormones control release of ant pit hormones
Hypophhyseal portal blood supply
All ant pit hormones control release of other hormones except for PRL
TSH
Thyroid stimulating hormone
Thyrotrope
FSH
Follicle stimulating hormone
Gonadotroph
LH
Lutenizing hormone
Gonadotroph
ACTH
Adrenocorticotropic hormone
Corticotrope
GH
Growth Hormone
Somatotroph
PRL
Prolactin
Lactotroph
PRL control
Inhibited by dopamine
Release stimulated by TRH and OT.
Levels rise after start of sleep and are lowest at midday.
PRL actions
Lactogenesis/lactation
Breast development
sleep
Reproduction
Ovulation
Most common secondary pituitary adenoma
Prolatinoma
FSH/LH control
Negative feedback from testosterone, estrogen, inhibin
FSH actions in men
Spermatogenesis in s in sertoli cells of testes which produce inhibin as negative feedback on FSH
FSH actions in women
Increases estrogen production from ovaries
LH actions in women
Induces ovulation in pulsatile fashion
Progestins
Female sex steroid.
Prepare uterine endometrium
Increase as result of LH surge and supported by corpus luteum
Estrogens
Female puberty
Menstrual cycle
Ovaries make greatest amount of estradiol
Androgens
Main male sex steroids
Testosterone is main circulating androgen
LH actions on men
Cause Leydig cells of testes to make testoasterone
GH control
Somatostatin inhibits release.
GH released in early morning
Releases stimulated by GHRH, hypoglycemia, serum arginine concentration, hunger from grhelin
GH actions
Stimulates growth of everything.
Stimulates secretion of IGF-1
GH deficiency
If before puberty, small stature.
If after puberty, obesity, dyslipidemia, depression.
Gigantism
GH excess before puberty
Acromegaly
GH excess after puberty
TH control
T3 and T4 negative feedback on hypothalamus and ant pit
TH actions
Increases basal metabolic rate
Increases sodium potassium pump activity.
Increases expression of beta adrenergic receptors.
Causes goiter if excess.
Releases calcitonin in response to hypercalcemia via c-cells
Hypothyroidism
Often autoimmune from thyroid peroxidase
Hyperthyroidism
Can be caused by thyroid stimulating immunogloubulin or TSH receptor Ab (grave’s disease)
Calcitonin
Released from C-cells.
Levels increase in response to high calcium levels in blood.
Lowers circulating calcium and phosphate levels.
Inhibits bone resorption.
Increases calcium excretion into urine.
High calcitonin
Associated with medullary cancer of thyroid
ACTH control of release
Stimulated by CRH from hypothalamus.
Highest levels in morning.
Negative feedback on CRH and ACTH from cortisol
ACTH actions
Stimulates adrenal glands to release corticosteroids to regulate metabolism and immune response.
Weakly stimulates aldosterone secretion
ACTH deficiency
Causes hypocortisolism (secondary addison’s disease).
Atrophy of flomerulosa, fasiculata, and reticularis
Cause deficiencies in glucocrticoids, adrenal anrogens, and mineralocorticoids
What part of adrenal gland is long-term responses
Cortex
What part of adrenal gland is immediate response
Medulla
Zona glomerulosa
Releases aldosterone (mineralocorticoid) to increases blood volume through water and Na retension
Zona fasciculata
Releases cortisol (glucocorticoid) for metabolic homeostasis and immunity
Zona reticularis
Releases DHEA (androgens) for development of sex hormones
Aldosterone control of release
Mineralocorticoid
RAAS (angiotensin II).
Hyperkalemia stimulates secretion.
ACTH weakly stimulates secretion
Aldosterone actions
Tells kidney to conserve water and sodium and get rid of potassium.
Increases blood volume.
Increases BP.
Can result in hypokalemia
Glucocorticoid control of release
Increases as result of stress.
Stimulatesd by ACTH from ant pit.
Glucocorticoid actions
Raise blood sugar.
Immune function suppression.
Pain reduction (steroid shot)
Glucocorticoid example
Cortisol
Cushing disease
Hypercortisolism.
Usually ACTH dependent
Addison’s disease
Cortisol difficiency
Adrenal androgen (DHEA) control of release
Stimulated by ACTH of ant pit.
Come from zona reticularis
Adrenal androgen (DHEA) actions
converted into estrogens in ovaries and testosterone in testes
DHEA deficiency in women
Decreased libido and pubic hair thinning
DHEA excess
Seen in congenital adrenal hyperplasia
Acne
Hirsutism
Virilization in women.
Most common cause of primary adrenal insufficiency
Addison’s disease.
Autoimmune where antibodies destroy adrenal gland
What is main causes of secondary adrenal insufficiency
prolonged exposure to glucocorticoid
Catecholamine control of releases
Come from adrenal medulla
Activates by sympathetic nervous system.
Cortisol stimulates epinephrine synthesis.
Catecholamine action
Increase cardiac output
Bronchodilation
Elevated blood glucose.
Catecholamine examples
Epi
Norepi
Glucocorticoid example
Cortisol
Parathyroid Hormone release control
Secreted by parathyroid glands.
Stimulated by hypocalcemia and hyperphosphatemia.
Inhibited by vitamin B
Parathyroid Hormone actions
Increase calcium and decreases phosphate.
Bone resorption of calcium into blood
Increases calcium absorption of intestine
Stimulate vitamin D synthesis at kidney
Hyperparthyroidism.
Hypercalcemia
Makes pt go crazy
Bones
Stones
Moans
Groans
Psychiatric overtones
Chvostek’s sign
Hypocalcemia.
Facial spasm from tapping gacial nerve anterior to ear
Trousseau’s sign
Hypocalcemia.
Carpal spasm in response to occlusion of brachial
What causes releases of amylin
Spikes in blood glucose
Amylin actions
Slows gastric emptying.
Increases satiety.
Inhibits glucagon secretion.
Muscarinic receptors on gastric glands
M1
Muscarinic receptors on parietal cells
M3
Heartburn/GERD meds
Antacids - mineral
H-2 receptor blockers - -dine
Proton pump inhibitor - -prazole
Peptic ulcer disease meds
Bismuth-based quad therapyy
Mucosal protective agents
Diarrhea meds
Opioid receptor antagonist
Antidiarrheal
Constipation meds
Stool softner
Osmotic laxatives
Stimulant laxatives
Bulk laxatives
What receptors stimulate H+/K+ pumps to pump acid into stomach
M3 - acetylcholine
H2- histamine
CCK-B - gastrin
Prostaglandin E2 (PGE2)
Decreases gastric acid secretion
Increases bicarbonate from epithelial cells, production of mucus, cell turnover, blood flow
GERD
Gastroesophagesal reflux disease.
Very frequent heartburn.
Esophageal sphincter isn’t tight enough
Acid neutralizers/antacid
Magnesium hydroxide
Calcium carbonate
Reduce pepsin activity.
Quick relief
Magnesium hydroxide
Antacid
Adverse effect is diarrhea.
Don’t use in pt with kidney problems
Calcium carbonate
Antacid
Adverse effect is constipation
Good calcium supplement
H-2 receptor blocker
-tidine
inhibit binding of histamine to parietal cells thus decreasing acid secretion.
Peaks in 1-3 hours
Very well tolerated
H-2 receptor blocker uses
GERD
Peptic ulcer disease
Acute stress ulcers through IV
Proton Pump Inhibitors (PPI)
-prazole
Prodrug
Superior to H-2 blockers in suppressing acid secretion and increasing peptic ulcer healing.
Enteric coating so it will survive acidity of stomach to be absorbed in small intestine
Heavy hitters
Proton Pump Inhibitor (PPI) method of action
Irreversibly bind and deactivate to H/K+ pump in parietal cells
Cimetidine
H-2 Receptor blocker
CYP 450 inhibitor (effects other drug metabolism)
Antiandrogenic effects
PPI uses
GERD
Peptic ulcer
H. pylori
Used when things get bad
Long term PPI use
Want to get them on an H-2 or something once healed bc of adverse effects.
Peptic ulcer
Breaks lining os stomach or duodenum
Caused by H. pyolori and NSAIDS
What is used to treat peptic uclers
PPI
H-2 blockers
Reduce intragastric activity
H. pylori
Gram negative
Requires antibiotic treatment
Transmitted orally.
Degrades mucosa
Causes ulcers
NSAID risks
Responsible for topical injury and effects.
Weak acids
If ulcer or opening in stomach/intestinal line they can cause problem.
Don’t cause opening themselves.
Decrease prostaglandin synthesis.
Thats why we take with food
H. pylori treatment
Bismuth-based quadruple therapy:
PPI
2 antibiotics
Bismuth subsalicylate
Non-H.pylori peptic ulcer disease treatment
PPI PO QD-BID to decrease acid secretion.
Antacid/acid neutralizer PRN.
Mucosal protective agentto protect while ulcer heals
Mucosal protective agents
Coating agents
Prostaglandin
Sucralfate
Coating agent to protect mucosa
Forms negatively charged gel that binds to positive proteins to adhere to epithelial cells while healing.
Doesn’t affect pH, just coats to protect while healing
Sucralfate
Mucosal protective agent
Prevents stress ulcers and treats duodenal ulcer
No toxicity
Causes constipation
Bismuth Subsalicylate (peptol bismol) as mucosal protective agent
Mucosal protective agent
Interacts with necrotic mucossal tissue and forms protective barrier to protect ulcer.
Inhibits pepsin and increases mucus to protect ulcer.
Stimulates secretion of PGE2 and bicarbonates.
Stops growth of H. pylori.
Black tongue and stool
Misoprostol
Mucosal protective agent
Inhibits histamine action at H-2 receptor.
Prevent NSAID induced ulcer
No pregnancy
Antimotility agents to fix diarrhea
Opioid receptor agonist
Fluid electrolyte transport modification to fix diarrhea
Bismuth subsalicylate
Opiod receptor agonist
For diarrhea
Loperamide
Diphenoxylate/atropine
Opioid receptor agonist method of action
Activate presynaptic opioid receptors in enteric nervous system.
Blocks ACh release.
Anti-SLUDGE
Anti-parasympathetic
Opioid receptor adverse effects
Toxic megacolon
So don’t give to pt if they have fever, severe abdominal pain, swollen abdomen
Loperamide
Opioid receptor agonist
Doesn’t cross BBB unless abused.
For acute/travelers diarrhea
Diphenoxylate/atropine
Opiod agonist.
Van cause headache, dry mouth, constipation
Atropine to discourage abuse
Controlled substance
Bismuth subsalicylate as antidiarrheal
Short term use
Avoid in kidney issues
How to prevent constipation
High fiber diet
fluid intake
Regular exercise
Don’t hold poop
Docusate
Stool softener
Allows water to penetrate oil layer around poop to soften stool
More preventative care than treatment
good after labor or at initiation of opioids
Cons of laxatives
Electrolyte imbalance in long term use.
Potential risk of dependency
Osmotic laxative
Water soluble
Nonabsorbable
Softens stool
Increases stool volume
Increases perstalsis
Polyethylene glycol (miralax)
Osmotic laxative
over the counter
Onset of action is 1-3 days
Simulant laxatives
Senna
Bisacodyl
Cause more urgent BM than osmotic laxatives
Senna
Stimulant laxative
Irritates luminal sensory nerves stimulating colonic motility and reducing colonic water reabsorption.
Bisacodyl
Stimulant laxatives
Prodrug converted in gut.
Increases water content of stool.
Expect BBM in 6-12 hours.
Bulk laxatives
Form gels in large intestine causing water retension stimulating stretch receptors and increasing peristalsis.
Onset is 1-3 days
For mild constipation
CAN CAUSE INTESTINAL BLOCK if not enough water ingested
Decrease absorption of other meds so give at different time
Methylcellulose
Bulk laxative
Less side effects
Psyllium husks
Bulk laxative
Gas, bloating, abdominal cramping.
Good for getting everything out bc husks scrape the sides of colon
ADH cellular effect on kidneys
Causes aquiporins to be expressed on cell membrane to take in water to then put back into blood rather than being excreted in urine
How do we measure GH in blood
IGF-1
What thyroid hormone is more metabolically active (potent)
T3 but T4 is made more bc thats how the chemistry work
We turn T4 into T3 in periphery
Rapid acting bolus meds
Insulin aspart
Insulin lispro
Insulin glulisine
Inhaled insuline
Done at meal time
TH replacement
Liothyronine
Levothyroxine
Desiccated thyroid
Agents for hypothyroidism
Thioamides
methimazole
propylthiouracil
What allows glucose to get into cells
Insulin unlocks GLUT-4 transport proteins
GLP-1
Glucose in intestine stimulates GLP-1 secretion GLP-1 binds to beta cells causing insulin to be released
What type of receptors are insulin receptors and what does their activation cause
Tyrosine kinase
So causes phosphoryaltion cascade and downstream effects.
Activation moves GLUT-4 transporters to surface
Basal insulin
Keeps glucose levels stable through fasting.
Always there no matter food
Bolus insulin
Responds to rise in blood glucose after food intake
How do we make insulin for injection
Recombinant DNA from bacteria
Why do we give insulin SQ
Its a polypeptide so it would denature in the stomach
Prandial
Insulin given around time of food
Short acting bolus meds
Reg human insulin
Intermediate Basal insulins
Insulin isophane suspension
Slow absorption longer duration
Long acting insulin
Insulin glargine
Insulin detemir
Insulin degludec
Human insulin analog
No true peak
Last long time
Insulin adverse effects
Hypoglycemia
Weight gain
Injection sight reaction
Glucagon meds
Generi glucagon emergency kit
Baqsimi
Gvoke hypopen
Given when blood sugar gets very low
Baqsimi
Glucagon nasal powder
Inhalation not required
More effective than glucagon
Easiest to use
Gvoke Hypopen
Gluvaon autoinjector
Like an epipen for glucagon
Meds that increase insuln secretion
Sulfonylureas
Glyburide
Glipizide
Glimepiride
Sulfonylureas
G drugs
Cause insulin secretion
Block ATP sensitive K channel in beta cells causing depolarization and infulx of calcium causing insulin secretion.
Glyburide
Sulfonylurea
Longest acting insulin secretion drug.
Greatest risk of hypoglycemia and weight gain.
Drugs that increases glucose-dependent insulin secretion
Hypoglycemia not as big of a risk
GLP-1 receptor agonist
GIP receptor agonist
DPP-4 inhibitors
Endogenous incretins
GLP-1
GIP
Secreted by gut after eating
Stimulate insulin secretion in response to high glucose
Inactivated by DPP-4
GLP 1 receptor agonist drugs
-atide or -glutide
Bind to GLP-1 receptor on beta cell activating signaling cascade increasing adenylyl cyclase and cAMP causing insulin release
GLP 1 receptor agonist adverse effects
-atide or -glutide
Box warning is thyroid c cell tumor risks
Tirzepatide
GLP-1/GIP receptor agonist
Binds to both receptors increasing glucose dependent insulin release
“twincretin”
More effective
Box warning for c-celll tumor risk
effect hormonal birth control
DPP-4 inhibitors
-gliptin
Blocks Dpp-4 enzyme slowing breakdown of GLP-1 increasing GLP-1.
Stimulates insulin release
NO effect on gastric emptying or satiety
Biguanide
Metformin
Decreases hepatic production of glucose
Decreases glucose absorption in gut.
Increases insulin sensitivity in muscle and fat.
Increases glucose uptake.
Take with food.
Biguanide (metformin) box warning
Metformin decreases hepatic uptake of lactate so lactic acidosis happens
Thiazolidinediones
-glitazone
Decrease hepatic glucose
Lowers tricglyceride
Increases HDL
Activate nuclear receptor causing expression of genes that code for glucose and lipid metabolism.
Box warning - CHF
Avoid in youth
SGLT2 inhibitors
-gliflozin
Increase renal excretion of glucose
Blocks SGLT-2 in PCT preventing glucose reabsorption causing glucose to be pissed out decreasing blood sugar
Can reduce CKD
Weight loss
Why do thyroid meds take so long to take effect
Act on DNA in nucleus
When should someone take thyroid meds
30 mins before first consumption of the day.
Need empty stomach
Levothyroxine
Synthetic T4
Stable
Cheap
No allergenic foreign proteins
Must be converted to T3 in body
Liothyronine
Synthetic T3
much more potent than levothyroxine.
Short half life so more doses.
Can easily put person into cardiotoxicity
Good for rapid onset or rapid termination
Desiccated thyroid
Natural pork thyroid
T4 and T3 in 4:1 ratio
Commonly recalled
Thioamides
Treat Hyperthyroidism
Prevent/interfere with hormone SYNTHESIS by inhibiting thyroid peroxidase.
Methimazole
Propylthiouracil
FDA pregnancy category D, but hyperthyroidism is also bad for pregnancy
Propylthiouracil (PTU)
Thioamide
Preferred in first trimester of preg
Box warning of severe hepatitis
Methimazole
Thioamide
More potent than PTU
